Several oxidative mechanisms for leukocytic destruction of pathogens have been identified, one of the most active of which involves reactions catalyzed by the enzyme myeloperoxidase (MPO) (donor: H2O2 oxidoreductase, EC 1.11.1.7). A number of chemical compounds arising from the catalyzed peroxidation of halide ions have been suggested to be microbicides; recent evidence from our laboratory strongly favors hypochlorous acid (HOCl) as a primary toxin. Experiments will be undertaken to (1) characterize the oxidative reactions of HOCl with components of microbial cell walls and membranes and susceptible enzymes under reaction conditions existing within the phagosome and (2) to seek evidence for the occurrence of these reactions during microbial digestion by polymorphonuclear leukocytes. Both reactivity and product identification studies will be made, using HOCl and the MPO-H2O2-Cl-system as oxidants. Results from these studies should improve our understanding of: (1) major toxins generated in the phagosomal reactions, (2) sites of oxidative attack on encapsulated cells and the sequential degradation process, and (3) the role played by MPO in disinfection, specifically, whether or not the enzyme directs oxidative degradation by substrate activation at specific sites on the cells.